Combinations of Thrombolytics with Platelet Glycoprotein Iibiiia Inhibitors and New Antithrombins

With the failure of new thrombolytic monotherapies to improve early coronary patency and clinical outcomes compared with tPA, interest has shifted toward combina tion pharmacotherapies (135). Theoretical arguments have been made for combining fibrinolytics with augmented antiplatelet therapies (136). The platelet membrane glycoprotein (GP) Ilb/IIIa, a specific fibrinogen receptor, is the final common pathway in platelet activation and an attractive therapeutic target. Antibodies, peptides, and small molecules have been developed that block the platelet GP IIb/IIIa receptor. These have potent platelet anti-aggregatory effects and have demonstrated efficacy in the setting of non-STE ACS and coronary angioplasty (137-140). In STE-AMI, their utility as adjunctive therapy for patients undergoing direct percutaneous transluminal coronary angioplasty (PTCA) with stenting recently has been shown (141). Given the critical role of platelets in coronary arterial thrombosis, the combination of a fibrinolytic with a GP IIb/IIIa inhibitor has substantial appeal as an approach to improving pharmacologic reperfusion. Results of the two large mortality trials of combination therapy are summarized in Table 5.

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